Viruses that infect humans and other animals present a difficult and complex area of medical research. Viruses lead to a range of diseases which can manifest as a result of infection.
In humans, some of the more well known viruses include Human Immunodeficiency Virus (HIV), Hepatitis and Herpes viridae (more commonly known as the Herpes viruses, which are a large family of DNA viruses that cause diseases in animals).
Within the Herpes virus family, about five members are predominantly found in humans. It has been reported that about 90% of all adults have been infected with at least one of the five viruses listed below:                Herpes simplex type 1 (HSV-1) which is known to cause orofacial lesions of a vesicular or ulcerative nature (i.e. cold-sores);        Herpes simplex type 2 (HSV-2) the predominant cause of genital herpes (although noting there is some cross-over between HSV-2 and HSV-1 in the two regions);        Varicella zoster virus which causes chicken-pox and shingles;        Epstein-Barr virus which causes mononucleosis;        Cytomegalovirus which causes symptoms similar to glandular fever.        
HSV-1 and HSV-2 are of particular concern to humans not only due to their prevalence, but also their social implications. HSV-2 is spread through sexual contact, and is often seen through the eyes of the public as a disease of the promiscuous. Therefore, those with HSV-2 are burdened with a virus which not only has many negative social connotations associated with it, but also cannot currently be cured, is a significant discomfort during outbreaks, and is contagious.
In the case of HSV-1, it is often associated with HSV-2 and genital herpes even though the viruses are different. Therefore there is a negative implication associated with cold-sores, despite in many cases not being linked to genital herpes. Regardless, owing to the fact that facial cold-sores are in full public view on a person's face, the condition can cause significant distress to the sufferer as well as being a physical discomfort.
Beyond the negative social implications and discomfort of the diseases of HSV-1 and HSV-2, more serious consequences can result from the viral infections. Neonatal herpes infections can be severe with up to 50% mortality for disseminated infection. The risk is more severe if the mother has a primary infection during pregnancy with HSV-1. It is also possible that HSV-1 and HSV-2 can lead to infection in the cornea (herpetic keratitis) and brain (encephalitis), and can lead to illnesses in HIV patients.
There are treatments available for HSV-1 and HSV-2 to alleviate the symptoms and to appearance of the diseases caused by the virus. For example, antiviral medications acyclovir, valacyclovir and famiciclovir are used for recurrent herpes infections. Yet, these do not provide a cure and there are often significant side effects with treatment. For example, for treatment of HSV-2, oral medication is recommended for the treatment of genital herpes, but this comes at the expense of considerable side effects as outlined in Beauman, J G. Genital herpes: a review. Am Fam Physician 2005; 72:1527-1534.
A further problem can be increased drug resistance. In Strand et al., Antimicrobial Agents and Chemotherapy Vol 56, No 11, it states that “The need for antiviral agents is apparent, since HSV isolates resistant to acyclovir treatment are frequently isolated in immune-compromised patients”.
Other treatments under research investigation include L-lysine, aspirin, or topical zinc treatment. Natural alternatives which are also under investigative studies include creams or gels containing licorice root (Glycrrhiza glabra), lemon balm (Melissa officinalis) or Aloe Vera (Aloe barbadensis). However, these approaches are still in their infancy and trials to support therapeutic effectiveness still need to be completed.
Although clinical trials are presently underway, there are still no vaccines currently available for Herpes simplex. Therefore, once a person is infected with the virus, he/she will be a carrier for life. Whilst some may present no or little symptoms, they still can infect others. Others, less fortunate, may present the disease phenotypes more frequently which can be a significant burden to the individual, both physically and emotionally.
A further problem with some compounds having anti-viral activity is that the compound can also displays strong cytotoxic characteristics. This means the compound kills host cells. Whilst this may be of benefit if the cell is infected with the virus, many compounds also are cytotoxic to healthy cells. For example, this disadvantageous trait is present in chemotherapy which by its very nature is cytotoxic.
Another problem which is seen with many anti-viral compounds, particularly for oral medications, is a low potency (often described as a high minimum inhibitory concentration, or MIC). This means that the patient must be administered higher amounts of the active compound to deliver the therapeutic result. This is disadvantageous as it can lead to more severe side effects from the compound or excipients in the medicament, can increase the cost and complexity of the manufacture of the medicament, and can lead to a lower shelf life of the product to due poor stability at higher concentrations. Therefore, there is a need to identify new compounds that have anti-viral activity and which preferably have a high potency, either on their own, or when synergistic combined with one or more other agents.
There has also been a focus over the past few decades to discover and use naturally available compounds as new anti-viral agents. The advantages of this approach can include:                Often the compound, and/or the source of the compound (e.g. a plant) has been used for other purposes and thus has a proven safety record and good public perception.        Avoids the need to do rational drug design which can cost significant amounts of research money and time.        A natural source of a compound or compounds is beneficial due to the ability to harvest large amounts of the source. Extracts of the source, or the pure compound(s) may then be used to develop suitable compositions and dosage regimes.        Knowledge of a naturally occurring compound displaying newly discovered anti-viral activity can be used as a platform for developing synthetic derivatives with improved pharmacokinetic features, such as improved potency, stability, or reduced side effects.        
It is an object of the present invention to address the foregoing problems or at least to provide the public with a useful choice.
All references, including any patents or patent applications cited in this specification are hereby incorporated by reference. No admission is made that any reference constitutes prior art. The discussion of the references states what their authors assert, and the applicants reserve the right to challenge the accuracy and pertinency of the cited documents. It will be clearly understood that, although a number of prior art publications are referred to herein, this reference does not constitute an admission that any of these documents form part of the common general knowledge in the art, in New Zealand or in any other country.
Throughout this specification, the word “comprise”, or variations thereof such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
Further aspects and advantages of the present invention will become apparent from the ensuing description which is given by way of example only.